Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy

Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised, at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases. Received: 4 October 1996 / Accepted: 6 December 1996     

Effects of smoking and drinking on excretion of hippuric acid among toluene-exposed workers

Summary In order to investigate possible effects of smoking and drinking on the metabolism of toluence in occupational settings, 206 toluene-exposed men (mean age: 31.4 years) in shoemaking, painting, or surface-coating workshops together with 246 nonexposed control men (36.8 years) were studied for the time-weighted average intensities of exposure to toluene, hippuric acid concentration in shift-end urine samples, and the two social habits of smoking and drinking. The mean daily consumptions of cigarettes and ethanol were about 20 pieces and 10 g among smokers and drinkers, respectively. The geometric mean toluene concentration among the exposed subjects was about 20 ppm, with a maximum of 521 ppm. Regression analysis after classification of the subjects by smoking and drinking clearly demonstrated that the two social habits, when combined, markedly reduce the hippuric acid level in the urine of workers exposed to was a significant association between smoking and drinking habits, which hindered separate evaluation of the effects of the two habits on toluene metabolism. Comparison of the present results with the findings reported in the literature, however, suggested that the observed effects may be attributable to smoking rather than to drinking habits.     

Antiherpes activity of chemically synthesized lipid A-subunit analogue GLA-60 in immunosuppressed mice

Intraperitoneal administration of 10 micrograms GLA-60, a chemically synthesized lipid A analogue, to mice one day after treatment with 200 mg/kg of cyclophosphamide (CY) significantly increased the number of macrophages, lymphocytes and polymorphonuclear leukocytes (PMNs) in the peritoneal cavity. The intrinsic antiviral activity of macrophages against herpes simplex virus type 1 (HSV-1) as well as natural killer (NK) activity against YAC-1 target cells was stimulated by administration of GLA-60 to CY-immunosuppressed mice. When the mice were administered GLA-60 prior to HSV-1 infection, virus growth was inhibited and the mortality rate of infected mice was reduced. Thus, GLA-60 is a potent immunomodulator achieving its antiviral action through enhancement of nonspecific host defense mechanisms. Combined treatment of GLA-60 with the antiviral agent acyclovir (ACV) resulted in greater protection against HSV-1 in the CY-immunosuppressed mice than did single treatment with either GLA-60 or ACV.     

Effect of repeated transcatheter arterial embolization on the survival time in patients with hepatocellular carcinoma. An analysis by the Cox proportional hazard model.

One hundred fifty-eight patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) as repeatedly as possible. Survival rates at the end of the first, second, and third year were 76.5%, 54.5%, and 41.1%, respectively. In 142 patients with repeated TAE, a significantly increased number of patients with complete necrosis of tumor was observed after repetition of the therapy. Adjusting the imbalance in prognostic factors among patients by using Cox proportional hazard model, it proved that the best response during the repeated therapy, rather than the first response, was significantly associated with survival period of the patients. Aside from the factor of response to the treatment, tumor size was the worst prognostic factor at the time when diagnosis was made. Other significant factors were portal vein invasion by HCC and bilirubin. The survival period of patients with HCC treated by repeated TAE was, therefore, affected by cancer factors, liver cirrhosis factors, and therapy-responsiveness factors. It is concluded that even if complete necrosis of tumor is not obtained after the first trial, repetition of TAE is an effective measure for prolonging of survival time in patients with HCC.     

Validity and reliability of the Japanese version of the Neuropsychiatric Inventory Caregiver Distress Scale (NPI D) and the Neuropsychiatric Inventory Brief Questionnaire Form (NPI-Q)]

OBJECTIVE: Neuropsychiatric disturbances are common and burdensome symptoms of dementia. Assessment and measurement of neuropsychiatric disturbances are indispensable to the management of patients with dementia. Neuropsychiatric Inventory (NPI) is a comprehensive assessment tool that evaluates psychiatric symptoms in dementia. We translated the NPI-Caregiver Distress Scale part of NPI (NPI-D) and NPI-Brief Questionnaire Form (NPI-Q) into Japanese and examined their validity and reliability. SUBJECTS AND METHODS: The subjects were 152 demented patients and the caregivers who lived with them. These patients consisted of 76 women and 76 men; their mean age was 73.9 +/- 7.8 (S.D.; range: 49 to 93) years. Their caregivers consisted of 46 men and 106 women; their mean age was 65.0 +/- 11.4 (S.D.; range: 35 to 90) years. The Mini-Mental State Examination (MMSE) was conducted with all patients and NPI-Q, NPI, NPI-D, and the Zarit caregiver burden interview (ZBI) were conducted with all caregivers. We examined validity of NPI-D by comparing its score with the MMSE and ZBI scores, and the validity of NPI-Q by comparing its score with the NPI and NPI-D scores. In order to evaluate test-retest reliability, NPI-D was re-adopted to 30 randomly selected caregivers by a different examiner one month later and NPI-Q was re-executed by 27 randomly selected caregivers one day later. RESULTS: Total NPI-D score was significantly correlated with ZBI (rs = 0.59, p < 0.01). Test-retest reliability of NPI-D was adequate (ri = 0.47, p < 0.01). Total NPI-Q severity score and distress score were strongly correlated with NPI (r = 0.77, p < 0.01) and NPI-D (r = 0.80, p < 0.01) scores, respectively. Test-retest reliability of the scores of NPI-Q was acceptably high (the severity score; ri = 0.81, p < 0.01, the distress score; ri = 0.80, p < 0.01). CONCLUSION: The Japanese version of NPI-D and NPI-Q demonstrated sufficient validity and reliability as well as the original version of them. These are useful tools for evaluating psychiatric symptoms in demented patients and their caregivers' distress attributable to these symptoms.     

Excitatory mechanism of deflationary slowly adapting pulmonary stretch receptors in the rat lung.

The excitatory responses of deflationary slowly adapting pulmonary stretch receptor (SAR) activity to lung deflation ranging from approximately -15 to -25 cm of H(2)O for approximately 5 s were examined before and after administration of flecainide, a Na(+) channel blocker, and K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 microg/kg), an Na(+) channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na(+) channels on the nerve terminals of deflationary SARs.     

A case report of spinal epidural Ki-1 lymphoma presenting acute paraplegia without spinal cord compression at the first onset]

A 68-year-old man noticed weakness in both legs, which worsened rapidly with additional urinary disturbance. At the time of admission, a neurological examination revealed spastic paraplegia. Sensation was intact. Magnetic resonance imaging (MRI) did not show any lesions in the spinal cord. Thereafter, sensory disturbance under Th5 level and weakness in both hands developed gradually. Seven months after the onset, he noticed pain of the right upper arm. MRI showed an epidural mass at the level between the lower cervical and the upper thoracic spine. Histological examination of the epidural mass revealed Ki-1 lymphoma. In this case, the diagnosis was difficult, because lymphoma did not present epidural mass in the early stage. We speculate that spinal epidural lymphoma might disturb venous circulation and cause myelopathy in this patient.     

Design of a Centrifugal Blood Pump with Magnetic Suspension

Abstract: A new concept blood pump, whose impeller is suspended by permanent magnets and a mechanical pivot without seals or ball bearings, is presented in this paper. The primary aim of the blood pump is an application to implantable artificial hearts. The prototype model is of a centrifugal type with a four-vaned semiopen impeller 50 mm in diameter. Since this mechanism has no seals or ball bearings, flow stagnation or heat generation that might cause blood cell denaturation is expected to be small. The results of performance testing for the prototype model 2 were satisfactory regarding pump head and efficiency. The radial-suspension magnets and the magnetic coupling were stable. As a result, the present mechanism has been verified to be a candidate applicable to implantable artificial hearts.